脂联素的信号转导通路

脂联素是一种由脂肪组织分泌的胶原样蛋白,其能降低血浆游离脂肪酸,具有抗动脉粥样硬化、改善胰岛素抵抗、降血糖、抗炎等作用,但其作用机制尚不十分明确。近期,脂联素的两型受体AdipoR1／R2已经被克隆,脂联素可能是通过其受体激活过氧化物酶体增殖物激活受体(PPAR)和AMPK信号转导通路而发挥作用。     

脂联素的研究进展

脂联素（adiponectin）是一种由脂肪细胞特异性高分泌,具有多种生物学功能的特殊蛋白质它直接作用于肝脏、骨骼肌和血管,能提高胰岛素敏感性,增强脂肪酸β氧化,抵制血管炎症反应,最新研究还发现脂联素和骨生成密切相关。与其它脂肪因子不同的是,循环中脂联素的浓度与人体脂肪含量成反比,会因TNF-α的作用而上调,会被噻唑烷二酮类药物所抑制,还受到胰岛素抵抗和炎症反应的影响脂联素受体有2类,分别为AdipoR1和AdipoR2,AdipoR1主要分布在骨骼肌上,AdipoR2则高表达于肝脏组织。本文主要综述了脂联素及其受体的结构、生物学功能和研究进展。     

儿童单纯肥胖症血清瘦素、脂联素相关性研究及意义

目的:检测单纯肥胖症患儿血清中瘦素、脂联素水平,评价其临床意义.方法:依据儿童单纯肥胖症诊断标准选取40名患儿,男女各20名,选取20名年龄、性别类同的健康儿童作为对照组.应用ELISA法检测患儿血清瘦素及脂联素水平,与健康儿童进行比较及男女两组之间比较.结果:与对照组相比,患儿血清脂联素水平降低,瘦素水平升高,差异有统计学意义(P<0.05),男女两组比较,差异无统计学意义(P>0.05).结论:肥胖症儿童脂联素、瘦素水平的变化与儿童肥胖症发病密切相关,对儿童肥胖症的发展趋势及预后判断有一定意义,脂联素、瘦素素水平是肥胖发生的预测指标.     

脂联素与胰岛素抵抗

胰岛素抵抗即胰岛素敏感性降低,是多种疾病,特别是糖尿病及心血管疾病共同的危险因素,是滋生多种代谢相关疾病的共同土壤。脂联素(adiponectin)是一种脂肪细胞特异性分泌的激素。近年来研究表明：脂联素具有促进血浆游离脂肪酸氧化、增加外周组织对胰岛素的敏感性、抑制肝糖输出和葡萄糖再生、抗动脉粥样硬化等功能。该介绍脂联素和胰岛素抵抗之间的关系,讨论其在治疗胰岛素抵抗和Ⅱ型糖尿病中的潜力。     

运动对老年肥胖大鼠脂联素的影响

目的：探讨运动对老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达、血浆脂联素浓度及胰岛素抵抗的影响。方法：取雄性SD大鼠,鼠龄21 d,分青春期、壮年期和老年期三个阶段喂养高脂饲料（脂肪率为36.3%~40.0%）,建立老年肥胖模型。鼠龄达到60周后,取自然生长老年大鼠随机分为对照组（C）和老年运动组（AE）,n=6;取老年肥胖大鼠随机分为肥胖对照组（OC）和肥胖运动组（OE）,n=6。动物跑台坡度0°,运动速度及时间为（15 m/min×15 min）,4组/次,组间休息5 min,每次共运动60 min,5次/周,持续运动8周。8周后,检测内脏脂肪组织脂联素mRNA和蛋白质表达,测定血糖、血浆脂联素浓度和胰岛素浓度,计算胰岛素抵抗。结果：运动干预后,与对照组比较,肥胖对照组大鼠脂联素mRNA和蛋白质表达显著减低,血糖浓度和胰岛素抵抗明显增高;而老年运动组大鼠脂联素mRNA和蛋白质表达显著增高。与肥胖对照组大鼠比较,肥胖运动组大鼠脂联素mRNA和蛋白质表达显著增高、血浆脂联素水平增高,血糖浓度和胰岛素抵抗明显减低。结论：老年肥胖大鼠内脏脂肪组织脂联素mRNA和蛋白质表达均降低,伴随胰岛素抵抗、血糖升高。运动能显著增加其内脏脂肪组织脂联素mRNA和蛋白质表达,升高血浆脂联素水平,改善胰岛素抵抗,降低血糖。     

脂联素基因单核苷酸多态性与Ⅱ型糖尿病合并肥胖及胰岛素抵抗相关联

脂联素是近年新发现的脂肪组织特异性的细胞因子,其mRNA是脂肪组织中含量最丰富的基因转录产物,该因子可通过多种途径影响个体对胰岛素的敏感性。脂联素基因多态性与肥胖、胰岛素抵抗和2型糖尿病密切相关,而与冠心病相关性研究的报道较少。本研究以中国汉族人群1,098例为对象,其中304例冠心病(CHD)患者,389例糖尿病患者(T2DM),及405例性别年龄相匹配的正常对照,采用PCR-RFLP技术对脂联素基因-4522C/T进行基因分型,并分别对血脂水平、胰岛素抵抗、体重指数等临床数据进行分析比较。研究结果显示,脂联素基因-4522C/T各基因型及等位基因在CHD组与对照组、T2DM组与对照组中的分布差异无显著性;经分组分析发现,T2DM合并肥胖患者BMI≥25kg/m2TT基因型及T等位基因明显多于对照组,差异有显著性,P=0.014和P=0.034;TT基因型T2DM患者胰岛素抵抗指数(HOMA-IR)显著高于携带有C等位基因的T2DM患者,P=0.0069。本研究提示脂联素基因-4522C/T与中国汉族人群T2DM合并肥胖的发生及T2DM患者胰岛素抵抗相关,是引发糖尿病患者肥胖和胰岛素抵抗的重要候选基因,而与冠心病的发生无关联。     

脂联素与肝源性糖尿病患者胰岛素抵抗的相关性研究

目的:探讨脂联素在肝源性糖尿病患者胰岛素抵抗中的作用.方法:检测肝源性糖尿病(A组)、肝硬化(B组)、2型糖尿病(C组)患者及正常人(D组)血清脂联素(ADPN)、空腹血糖(FPG)、空腹胰岛素(FINS)水平,计算其胰岛素抵抗指数(HOMA-IR)、β细胞功能指数(FBCI)、胰岛素敏感性指数(ISI),分析ADPN与胰岛素抵抗的相关性.结果:A组ADPN水平低于B组、D组(P<0.05);FPG水平低于C组(P<0.05);FINS,FBCI水平高于C组及D组(P<0.05);ISI低于D组(P<0.05);HOMA-IR显著高于B组及D组(P<0.05).ADPN与 FPG、FINS、HOMA-IR呈负相关;与ISI呈正相关.结论:肝源性糖尿病患者ADPN水平下降,其与胰岛素抵杭呈负相关,提示脂联素可能在肝源性糖尿病患者胰岛素抵抗中起着重要作用.     

脂联素基因多态性、肿瘤坏死因子-α与儿童肥胖症

脂联素(ADPN)是一种主要由脂肪细胞分泌的特异性细胞因子,参与机体的糖和脂肪代谢,随着脂肪组织的增多ADPN水平下降。人群中脂联素基因序列中存在相当数量的等位基因单核苷酸多态性(SNPS),脂联素基因的SNPs与儿童肥胖关系密切。肥胖儿童中肿瘤坏死因子-α(TNF-α)水平升高,限制肥胖的发展。脂联素和肿瘤坏死因子-α在机体内可相互影响表达,共同参与儿童肥胖的形成。     

大鼠胰岛素抵抗形成中脂联素受体基因表达及运动的影响

目的:检测SD大鼠脂联素受体的分布,观察大鼠胰岛素抵抗(IR)形成中脂联素受体(Adipok)基因表达及运动的影响。方法:46只雄性SD大鼠随机分为4组(n=12),以高脂膳食喂养诱导IR,同时运动组实施10周游泳运动干预。结果:AdipoR1/R2mRNA分别在骨骼肌和肝脏高表达(P<0.05);H组骨骼肌AdipoR1和肝脏AdipoR2mRNA表达显著低于C组(P<0.05)。结论:骨骼肌和肝脏AdipoR1/R2mRNA表达的下调可能是高脂大鼠IR形成的机制之一,未观察到运动干预的显著影响。     

脂联素的研究进展

脂联素(adiponectin)是一种由脂肪细胞特异性高分泌,具有多种生物学功能的特殊蛋白质.它直接作用于肝脏、骨骼肌和血管,能提高胰岛素敏感性,增强脂肪酸β氧化,抵制血管炎症反应,最新研究还发现脂联素和骨生成密切相关.与其它脂肪因子不同的是,循环中脂联素的浓度与人体脂肪含量成反比,会因TNF-α的作用而上调,会被噻唑烷二酮类药物所抑制,还受到胰岛素抵抗和炎症反应的影响.脂联素受体有2类,分别为AdipoR1和AdipoR2,AdipoR1主要分布在骨骼肌上,AdipoR2则高表达于肝脏组织.本文主要综述了脂联素及其受体的结构、生物学功能和研究进展.     

2型糖尿病脑梗死患者血浆血栓调节蛋白水平及其临床意义

目的：探讨血浆可溶性血栓调节蛋白（soluble thrombomodulin,sTM）与2型糖尿病脑梗死（type 2 diabetes mellitus cerebral infarction,DMCI）的关系及其临床意义。方法：选择2011年12月至2012年8月我科收治的急性脑梗死（acute cerebral infarction,ACO患者60例,其中DMCI患者30例,非2型糖尿病合并脑梗死（non—diabetes mellitus cerebral infarction,NDMCI）患者30例,以及同期健康体检者30例。采用酶联免疫吸附法（ELISA）检测其血浆sTM水平,并按美国国立卫生研究所脑卒中评分（NIHSS）进行临床神经功能缺损评估。结果：（1）与正常对照组相比,DMCI组及NDMCI组患者血浆sTM水平均明显升高,差异有统计学意义fP〈0．01）;（2）DMCI组患者血浆sTM水平和NIHSS评分均较NDMCI组显著升高,差异有统计学意义（P〈0．01）;（3）DMCI组和NDMCI组患者血浆sTM水平与NIHSS评分呈显著正相关,（r=0．785,P〈0．001）。结论：2型糖尿病脑梗死患者血浆sTM水平较正常人群显著升高,且与其神经功能缺损的严重程度呈显著正相关,检测血浆STM水平可有助于评估2型糖尿病合并脑梗死的分期、严重程度及其转归。     

2 型糖尿病脑梗死患者血浆血栓调节蛋白水平及其临床意义

目的：探讨血浆可溶性血栓调节蛋白(soluble thrombomodulin,sTM) 与2 型糖尿病脑梗死(type2 diabetes mellitus cerebral infarction,DMCI)的关系及其临床意义。方法：选择2011 年12 月至2012 年8 月我科收治的急性脑梗死(acute cerebral infarction, ACI)患者60 例,其中DMCI患者30 例,非2 型糖尿病合并脑梗死(non-diabetes mellitus cerebral infarction,NDMCI)患者30 例,以 及同期健康体检者30 例。采用酶联免疫吸附法(ELISA)检测其血浆sTM水平,并按美国国立卫生研究所脑卒中评分(NIHSS)进行 临床神经功能缺损评估。结果：(1)与正常对照组相比,DMCI组及NDMCI组患者血浆sTM 水平均明显升高,差异有统计学意义 (P<0.01);(2)DMCI 组患者血浆sTM 水平和NIHSS评分均较NDMCI 组显著升高,差异有统计学意义(P<0.01);(3)DMCI 组和 NDMCI组患者血浆sTM水平与NIHSS 评分呈显著正相关,(r=0.785,P<0.001)。结论：2 型糖尿病脑梗死患者血浆sTM水平较正 常人群显著升高,且与其神经功能缺损的严重程度呈显著正相关,检测血浆sTM 水平可有助于评估2 型糖尿病合并脑梗死的分 期、严重程度及其转归。     

Relationship between Plasma Adiponectin Levels and Metabolic Risk Profiles in Taiwanese Children

Objective: Adiponectin, a novel adipokine with antiinflammatory and insulin‐sensitizing properties, has an important role in glucose metabolism and is negatively correlated with body fat amount in adults. The purpose of this study was to evaluate the association of plasma adiponectin level with metabolic risk profiles and insulin resistance status among Taiwanese children. Research Methods and Procedures: We enrolled 1248 children (608 boys and 640 girls) to ascertain their demographic, anthropometric, and cardiovascular risk factors distribution in Taipei. We measured plasma insulin, adiponectin, and leptin levels by radioimmunoassay (Linco Research Inc, St. Charles, MO). We calculated an insulin resistance index (IRI) using the Homeostasis Model Assessment model and also calculated an insulin resistance syndrome (IRS) summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure, serum triglyceride, high‐density lipoprotein‐cholesterol (HDL‐C) (inverse), and insulin levels. Results: In general, the boys had larger BMI, higher systolic blood pressure, serum total cholesterol, and triglyceride, and lower plasma leptin and adiponectin levels than girls. Plasma adiponectin levels were correlated negatively with BMI, leptin, insulin, IRI, and IRS summary score but positively correlated with HDL‐C in both boys and girls. In multivariate regression analyses, adiponectin was negatively associated with insulin (girls only), IRI (girls only), and IRS score, and positively associated with HDL‐C in both genders even after adjusting for age, BMI, plasma leptin level, and other potential confounders. Discussion: These data suggest that plasma adiponectin levels were negatively associated with metabolic risk profiles that may have played a protective role in the development of insulin resistance among Taiwanese school children.     

Decrease in Serum Adiponectin Level Due to Obesity and Visceral Fat Accumulation in Children

Objective: To determine whether serum adiponectin is decreased in obesity and is restored toward normal level after treatment in children. Research Methods and Procedures: Subjects were 53 Japanese obese children, 33 boys and 20 girls (6 to 14 years old), and 30 age‐matched nonobese controls for measuring adiponectin (16 boys and 14 girls). Blood was drawn after an overnight fast, and the obese children were subjected to anthropometric measurements including waist and hip circumferences and skinfold thicknesses. Paired samples were obtained from 21 obese children who underwent psychoeducational therapy. Visceral adipose tissue area was measured by computed tomography. Adiponectin was assayed by an enzyme‐linked immunosorbent assay. Results: The serum levels of alanine aminotransferase, uric acid, triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol, total cholesterol/high‐density lipoprotein‐cholesterol, apo B, apo B/apo A₁, and insulin in obese children were higher than the reference values. Serum adiponectin level was lower in the obese children than in the controls (6.4 ± 0.6 vs. 10.2 ± 0.8 mg/L, means ± SEM, p < 0.001). In 21 obese children whose percent overweight declined during therapy, the adiponectin level increased (p = 0.002). The adiponectin level was correlated inversely with visceral adipose tissue area in obese children (r = ?0.531, p < 0.001). The inverse correlations of adiponectin with alanine aminotransferase, uric acid, and insulin were significant after being adjusted for percentage overweight, percentage body fat, or sex. Discussion: Serum adiponectin level is decreased in obese children depending on the accumulation of visceral fat and is restored toward normal level by slimming.     

PCT及CRP在急性肠梗阻大鼠血清中的表达水平及其临床意义

目的:探讨降钙素原(Procalcitonin,PCT)及C反应蛋白(C-reactive protein,CRP)在急性肠梗阻大鼠血清中的水平及其临床意义。方法:将83只Wistar大鼠分为对照组(n=13)、假手术组(n=35)和急性肠梗阻组(n=35)。对照组大鼠采集标本后处死,肠梗阻组行开腹手术结扎回肠末端,假手术组仅行开腹手术。检测8 h、24 h、48 h、72 h及96 h血清PCT及CRP水平,观察急性肠梗阻大鼠回肠组织的病理学改变情况。结果:假手术组PCT与CRP水平在术后24 h内显著升高,48 h至96 h逐渐下降;各时间点PCT水平明显高于对照组,而CRP水平在实验结束时已恢复至正常水平。肠梗阻组PCT和CRP水平在各时间点均明显高于对照组,并逐渐增加,到实验结束时达到高峰;肠梗阻组PCT和CRP水平在48 h-96 h均显著高于假手术组,差异具有统计学意义(P0.05)。组织病理学检查显示,对照组大鼠肠壁粘膜结构正常,假手术组可见轻度病理改变,肠梗阻组大鼠回肠组织可见粘膜结构明显破坏,绒毛坏死,严重水肿和炎症细胞浸润。结论:血浆PCT和CRP水平能够反映肠梗阻的状态和肠粘膜受损程度。     

Plasma Level of Adrenomedullin Is Influenced by a Single Nucleotide Polymorphism in the Adiponectin Gene

Objective

Adrenomedullin (ADM) and adiponectin are both involved in inflammation and cardiovascular diseases. The plasma levels of these peptides are influenced by single nucleotide polymorphisms (SNPs) in the ADM and ADIPOQ genes respectively. There is some evidence that ADM may regulate adiponectin gene expression, but whether adiponectin can regulate ADM expression is unclear, and was therefore investigated.

Methods

Plasma ADM level was measured in 476 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2). We genotyped them for 2 ADIPOQ SNPs that are known to be associated with plasma adiponectin level.

Results

The minor allele frequencies of ADIPOQ SNPs rs182052 and rs12495941 were 40.6% and 42.2% respectively. Plasma ADM level was significantly associated with rs182052 after adjusting for age and sex (β = 0.104, P = 0.023) but not with rs12495941 (β = 0.071, P = 0.120). In multivariate analysis, plasma ADM level increased with the number of minor alleles of rs182052 (P = 0.013). Compared to subjects with GG genotype, subjects with AA genotype had 17.7% higher plasma ADM level (95% CI: 3.6%–33.7%). Subgroup analysis revealed that the association was significant in diabetic patients (β = 0.344, P = 0.001) but not in non-diabetic subjects.

Conclusion

Plasma ADM level is related to SNP rs182052 in the ADIPOQ gene. Our findings provide new evidence of the interplay between these two important peptides in cardiovascular disease and diabetes. Knowing the genotype may help to refine the interpretation of these biomarkers.     

哈萨克族原发性高血压患者血浆CGRP水平及其相关性研究

目的:探讨血浆降钙素基因相关肽(CGRP)水平与新疆哈萨克族(哈族)原发性高血压病患者血压、血脂、血糖、肥胖等的相关性。方法:选取新疆哈族原发性高血压患者52例为观察组,哈族健康对照组48例,测量血压(BP)、身高、体重、腰围(WC)、臀围(HC),抽取空腹静脉血测定血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),计算体重指数(BMI)腰臀比(WHR)。结果:①原发性高血压组血浆CGRP水平明显低于对照组,差异有统计学意义(p<0.01);②原发性高血压组血浆CGRP水平与SBP、LDL-C和TG呈显著负相关(p<0.01);对照组血浆CGRP水平与SBP和LDL-C呈显著负相关(p<0.01)。结论:哈族原发性高血压患者血浆CGRP水平与血压、血脂存在相关性。     

2 型糖尿病患者血浆成纤维细胞生长因子-21 水平的变化及意义

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血浆成纤维细胞生长因子-21(fibroblast growth factor 21,FGF-21)水平变化以及观察短期胰岛素强化治疗对FGF-21水平的影响。方法:选择我院2013年1月至2015年1月收治的T2DM患者64例,其中初诊T2DM患者32例(T2DM组),T2DM合并大血管病变患者32例(合并大血管病变组),并选择同期体检健康者30例(对照组)。采用酶联免疫法测定三组血浆FGF-21水平以及胰岛素强化治疗前后的变化,分析血浆FGF-21水平与体质量指数(BMI)、腰臀比(WHR)、血脂、血糖、空腹血浆胰岛素(FINS)和糖化血红蛋白(Hb A1C)等水平的关系。结果:T2DM组及T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于对照组(P0.05),T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于T2DM组和对照组(P0.05)。空腹血浆FGF-21水平与T2DM患者FPG、Hb A1C水平呈明显正相关,WHR、舒张压、Hb A1C是影响血浆FGF-21水平的独立相关因素。经胰岛素强化治疗后,血浆FGF-21水平较治疗前明显下降(P0.05)。结论:T2DM患者血浆FGF-21水平明显升高,可能参与了T2DM及其大血管病变的发生和发展,胰岛素强化治疗可明显降低T2DM患者血浆FGF-21水平,血浆FGF-21可能作为T2DM病情和疗效评估的参考指标。     

冠状动脉旁路移植患者围术期的BNP 水平变化及临床意义

目的:研究冠状动脉旁路移植手术后患者B型脑钠钛(BNP)水平变化规律及临床意义。方法:选取我院2014年6月到2015年6月间收治的冠状动脉旁路移植手术患者80名,根据患者心脏左心室射血分数(LVEF)分为A组(45%)和B组(≤45%),观察两组患者在不同时间的BNP水平,对比两患临床相关指标、及心房颤抖和心功能不全发生情况。结果:A组患者在血管活性物质使用量、呼吸机使用时间、监护室停留时间及心房颤抖和心功能不全发生率都明显小于B组,差异有统计学意义(P0.05);术后6h两组患者的BNP水平开始明显上升,在术后24h达到峰值,此后开始下降但仍维持较高水平,组内比较差异均有统计学意义(P0.05)。A组患者在术前及术后各个时间段内BNP水平均明显小于B组,组间比较比较均有统计学意义(P0.05)。结论:冠状动脉旁路移植患者围手术期BNP水平可以反应患者心脏功能状况,BNP水平越高表示患者心脏越差。     

Plasma Adiponectin Levels in Overweight and Obese Asians

Objective: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. Research Methods and Procedures: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) ≥ 23 kg/m²], including 47 subjects with morbid obesity (BMI ≥ 40 kg/m²). Results: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. Discussion: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation.